Potential factors in carcinogenesis and tumor regression.

Known and unknown host factors determine the individual susceptibility to carcinogenic agents. Such factors may interact with either the phase of transformation (initiation) or with the phase of proliferation (promotion). Some of these factors have been recognized as potential determinants of the degree of susceptibility or resistance to cancer. Transformation may be impeded by a low rate of absorption of carcinogenic agents (barrier effect), by the availability of deactivating enzymes operative at several steps of the metabolism of carcinogenic agents, and by a high repair capability of DNA damage. Proliferation of transformed cells may be impeded or prevented by immune defense mechanisms and by maturation factors such as nerve growth factor (NGF), glia maturation factor, fibroblast growth factor, and others. NGF has already been shown to be capable of maturing anaplastic glioma cells (clone F98) and reducing their rate of growth. Rats treated with NGF following implantation of anaplastic glioma cells had a significantly decreased tumor growth rate and increased survival time. NGF administration to pregnant rats preceding exposure to ethylnitrosourea (ENU) (50 mg/kg, 21st day of gestation) or to offspring transplacentally exposed to ENU resulted in reduction of neurinoma development. The importance of NGF as a suppressing agent of neoplastic proliferation and as a prospective tumor therapeutic needs further exploration.